N-methyl-2-pyrrolidone (NMP) is produced in large quantities worldwide and is commonly used as an organic solvent in various industries, such as the petrochemical, surface treatment, and pharmaceutical industries or used as a cleaning agent in process equipment [[1], [2], [3]]. NMP has a specific concentration limit of 5 % in cosmetics [4]. It is a polar solvent that is miscible with several other organic solvents and with water as well. In addition, NMP is utilized in lithium-ion batteries and other hybrid batteries using lithium-nickel-manganese-cobalt oxide. It is used to make cathodes in lithium-ion batteries [[5], [6], [7]]. The increasing demand for electric devices and cars resulted in increased production of batteries worldwide. Therefore, the use of NMP became more prevalent.

Even though several chemical or biological degradation processes exist for reducing NMP concentrations in the post-use phases, the large consumption of NMP has raised concern regarding its potential presence in the environment. In the case of chemical degradation, photolysis (ozone treatment) has a lower efficiency [[8], [9]] in NMP abatement than photocatalysis [10], or the combined treatment with UV-C activated peroxymonosulfate [8] which results in the complete degradation of NMP. Moreover, NMP is 100 % biodegradable [[11], [12], [13]]. 5-OHNMP is a human metabolite of NMP, 43.8 % of NMP are excreted as 5-OHNMP with elimination half-times of ∼ 4 h [14].

Recently, NMP has come into focus due to its teratogenic effects. However, such a harmful property has not been unequivocally confirmed so far [4]. The U.S. Environmental Protection Agency (EPA) conducted a first-tier analysis to estimate NMP surface water concentrations and did not identify risks from incidental ingestion or dermal contact during swimming [15]. However, the European Union (EU) demonstrated that action on a Union-wide basis is necessary to address risks to the health of workers exposed to NMP [16]. NMP is classified as toxic for reproduction (category 1B) in accordance with Regulation (EC) No 1272/2008 of the European Parliament [17]. A recent study showed its toxic effects and NMP may become a contaminant of emerging concerns [3].

There are significant efforts being made to analyse NMP in environmental samples including water media. As yet no individual maximum level for NMP in water has been established, thus, NMP is being analysed to the lowest LOQ. Gas chromatographic (GC) methods coupled with nitrogen–phosphorus (NPD), flame ionization (FID); flame thermionic (FTD) or mass spectrometric (MS) detectors have been applied most commonly for NMP analysis in various samples [[18], [19], [20]], while the HPLC methods utilize tandem mass spectrometric detection [[21], [22], [23], [24], [25], [26]].

The chromatographic techniques enable reaching LOQs between 1.0 ng/mL and 1000 ng/mL for NMP or 5-OHNMP in body fluids (urine, plasma), plant-derived agro-products, pharmaceutical products, and biofilms. In the literature, earlier published methods for NMP and/or 5-OHNMP in water samples are almost non-existent. The LOQs reported in non-published methods, attained by laboratories accredited for analysis of NMP in water, are between 10.0 ng/mL and 1000 ng/mL using GC–MS or LC-MS/MS separations [27]. Generally, the LC-MS/MS methods for NMP offer lower LOQ’s than those of GC–MS techniques. The GC methods require sample preparation including liquid-liquid extraction (LLE) or solid-phase extraction (SPE) prior to the instrumental analysis. Also, precolumn derivatisation is usually needed using bis(trimethylsilyl)trifluoroacetamide [24]. The present study eliminated these time-consuming steps by applying an LC-MS/MS method. The challenge in HPLC separation is to obtain appropriate retention for 5-OHNMP (Fig. 1), which is a more polar (log P = −0.9) than NMP, and consequently has a low retention on reversed-phase (RP) columns [25]. Therefore, modified C18 HPLC or HILIC columns could provide appropriate retention for NMP and its metabolite [26].The required LOQ for monitoring several environmental chemical pollutants like pesticides, and pharmaceutical residues is generally 0.1 ng/mL in water [28,29]. Even though NMP maximum levels in water samples are not regulated at the present time, it is imperative to develop state-of-the-art methods, which could detect the lowest possible concentrations of these pollutants in the environment. Therefore, in the current research, we developed a sensitive LC-MS/MS method in combination with isotope dilution (ID) to quantify NMP and 5-OHNMP (Fig. 1) in water at sub-ng/mL levels. The aim of the study was to (i) optimize the RP HPLC separation for the simultaneous analysis of the two target analytes, (ii) compare RP and HILIC separations for these two compounds, (iii) achieve an LOQ as low as possible for NMP and its hydroxy metabolite by fine-tuning the MS/MS detection on various instruments, (iv) develop a sample preparation process allowing for the quick and simple sample pre-concentration, (v) evaluate the method performance characteristics in a single-lab method validation, and finally, (vi) apply the method on real water samples.